The systematic administration of drug agents, such as by transoral or intravenous means, treats the body as a whole even though the disease to be treated may be localized. When a disease to be treated is localized, a localized delivery of the drug agent is often the more advantageous approach. Moreover, certain invasive treatments require the insertion and expansion of stent devices in blood vessels, urinary tracts or other locations difficult to otherwise access. Conventionally, such stents are delivered to a location of interest utilizing a vascular catheter, or similar transluminal device. The stents may be medically-coated for localized delivery of one or more therapeutic agents.
U.S. Pat. No. 6,120,536, incorporated herein by reference for background information, discloses a type of self-expanding stent having a flexible tubular body formed of several individual flexible thread elements each of which extends in a helix configuration with the centerline of the body serving as a common axis. The treated elements are wound in the same direction but are displaced axially relative to each other and meet, under crossing, a like number of elements also so axially displaced, but having the opposite direction of winding. This configuration provides a resilient braided tubular structure which assumes stable dimensions upon relaxation. Axial tension produces elongation and corresponding diameter contraction that allows the stent to be mounted on a catheter device and conveyed through the vascular system as a narrow elongated device. Once tension is relaxed in situ, the device at least substantially reverts to its original shape.
Implanted stents have been used to carry medicinal agents, such as thrombolytic agents. For example, U.S. Pat. No. 5,163,952 to Froix discloses a thermal memoried expanding plastic stent device formulated to carry a medicinal agent in the material of the stent itself. Pinchuk, in U.S. Pat. No. 5,092,877, discloses a stent of a polymeric material which may have a coating associated with the delivery of drugs. Other implantable devices can include bio-active agents such as therapeutic and medicinal compositions designed to combat a particular ailment. Stents can also include a DNA coating for gene therapy to serve diverse medical purposes, including slowing down growth of certain cells. Genes are usually delivered into the patient's cells through a vector, such as a retro virus having genetically engineered DNA to include a desired DNA sequence. In the context of angioplasty, incorporation of appropriate DNA into the coronary artery walls near the treatment site can be beneficial to inhibit restenosis.
Thus, stents and other similar implants have been used as the delivery vehicle for the DNA or therapeutic agent. The stent provides the additional advantage of resisting artery reclosure by recoil after the expansion of the vessel wall. In this application, it is desirable to have the plasmid DNA or therapeutic agent released and expressed over a predetermined period of time in the target area.
in some cases, the delivery of DNA or therapeutic agent can be inefficient, requiring large amounts of DNA and long delivery times for the stent to be an effective delivery system. This in turn can require large amounts of polymer coating on the stent, adapted to hold and release the DNA over the required period of time. However, if the coating is too thick, expansion of the stent can cause cracking of the coating, thus reducing the effectiveness of the coating. In addition, excessive coating may also cover the windows formed in the stent between the wires forming the stent, which normally allow passage of oxygen into the walls of the artery. On the other hand, if the coating is too thin, the entire supply of DNA or the therapeutic agent can be released within a short frame of time.
Thus, controlled drug delivery from medical device coatings remains difficult to control and fine tune. As described, the conventional technologies rely on bulk phase release of therapeutic agents from carrier coatings. In this manner, often a rapid burst of the therapeutic agent occurs. Thus far the modification of release profile has been restricted to formulation chemistry changes. This strategy that has proven ineffective in controlling the drug release profile.